Aging Theory — Telomeres Theory
Although we have not identified the genes controlling human life span, there is a genetic element called a telomere that clearly regulates the replicative life span of human cells in culture. A telomere is a simple DNA sequence that is repeated many times, located at the tips of each chromosome. Telomeres are not genes, but they are needed for the proper duplication of the chromosomes in dividing cells. Each time the chromosomes are duplicated, the telomeres shrink a bit, until they get so short the DNA replication machinery can no longer work. This occurs because the enzyme that duplicates the DNA (DNA polymerase) has to have some portion of the chromosome out ahead of it.
Much like a train backing up on a track, DNA polymerase preserves a safe distance from the end of the DNA so it does not slip off the end. Telomeres also provide a guarantee that genes close to the ends of the chromosomes have been replicated. DNA polymerase stalls automatically whenever it gets too close to the end of the chromosome, permanently blocking the ability of the cell to divide. When this happens, the cell is said to have reached replicative senescence.
The telomeres in human fibroblasts are long enough to permit about 50 rounds replication of DNA. That is, the cell can divide about 50 times in culture. This is often referred to as the Hayflick limit, after Leonard Hayflick, the scientist who was the first to notice that normal cells cannot divide indefinitely in culture.
Cancer cells, on the other hand, can divide indefinitely, and from them scientists isolated an enzyme called telomerase that restores the telomeres after each cell division. If the telomerase gene is added to normal fibroblasts, they are no longer bound by the Hayflick limit and can divide indefinitely, like an immortal cancer cell.
The transformation of normal fibroblasts with the telomerase gene was conducted for the first time in 1998 at the Geron Corporation, a biotechnology company. The results generated a tremendous amount of excitement, for they seemed to imply that reversal of replicative senescence would be followed very quickly by the reversal of the aging process. Scientists at Geron began talking about human life spans of several hundred years.
Experiments since have shown, however, that while telomerase can block replicative senescence in cultured cells, it has little to do with the life span of the animal as a whole. Indeed some animals with long life spans have short telomeres and negligible telomerase activity, while other animals with short life spans have long telomeres and active telomerase. This is not surprising if we keep in mind that most cells in an animal’s body are postmitotic; they stop dividing soon after the individual is born. So individual life span made from those cells cannot be regulated by the length of the telomeres.